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““The scorpion envenoming syndrome is an important worldwid

““The scorpion envenoming syndrome is an important worldwide public health problem due to its high incidence and potential severity of symptoms (Ministério

da Saúde, 2009 and Ministério da Saúde, 2013). It occurs mainly in tropical and subtropical countries, where hot and humid http://www.selleckchem.com/products/Vincristine-Sulfate.html weather favors the scorpion proliferation. Tityus serrulatus, the scorpion of larger medical importance, is responsible for the most serious accidents ( Fundação Nacional de Saúde, 2001). Its venom is composed of a complex mixture of toxic and non-toxic peptides ( Diniz and Gonçalves, 1960). Two types of scorpion toxins have been implicated in the toxicity: toxin gamma (TiTx, a β-type toxin) and tityustoxin (TsTX, an α-type toxin), both with specific affinity to voltage-gated sodium channels (VGSC) ( Barhanin et al., 1982). Because TsTX was suggested as one of the higher lethal components of the T. serrulatus venom ( Kalapothakis and Chavez-Olortegui, 1997), it was chosen to be tested in this study. The TsTX binds to the site 3 of VGSC, mainly in the activated state, delaying

activity is generated and modulated by various central nuclei ( Guyenet, 2006). The direct action of scorpion venom on the central nervous system (CNS) has been neglected due to the understanding that its toxic proteins would not be able to across the blood–brain barrier (BBB) ( Ismail et al., 1974 and Revelo et al., 1996). However, biodistribution assays detected the systemically given labeled toxin in the CNS of developing animals, whose BBB is still immature ( Clot-Faybesse et al., 2000 and Nunan et al., 2003). Additionally, Nunan and colleagues observed that the TsTX distribution in the brain of young rats was about threefold that of an adult. Moreover, the CNS seems to be very sensitive to TsTX ( Nunan et al., 2003). In fact, there is an overwhelming literature about the TsTX effects in the CNS: (a) intracerebroventricular (i.c.v.) of TsTX induced convulsions in rats ( Lima et al., 1975); (b) microinjections of TsTX into hippocampus of rats undergoing electroencephalographic (EEG) recordings induced epileptiform discharges ( Sandoval and Lebrun, 2003); (c) intracerebroventricular (i.c.v.) injection of TsTX low dose (1.